The project is aimed at the determination, definition and integration of the immunological factors involved in the host defenses against mammary tumors. Several types of antigens may have relevance in the outcome of the oncogenic disease, i.e. virus-associated, virus-induced and non-viral tumor associated antigens. Three syngeneic mouse model systems will be employed: 1) mouse mammary tumor virus (MMTV)-non virion expressing Balb/cCrgl mice implanted with MMTV-negative chemically-induced mammary tumors of different immunogenic potentials; 2) MMTV-positive Balb/cfC3H mice with MMTV-positive mammary tumors of spontaneous appearance (SMT) in this strain and 3) Blab/c mice with inherited asplenia and heterozygous for the nude hene which have a high incidence of SMT at an early age. The spleen cell subpopulations involved in the responsiveness to MMTV and tumor associated antigens (TAA) will be analyzed by means of various cell surface markers such as presence of surface immunoglobulin, Thy 1.2, Lyt-1, and Lyt-2 antigens and Fc receptors and complement receptors. The expression of MMTV antigen(s) in the lymphoid cells will be monitored with monoclonal antibodies against subviral particles. Functional reactivities of the lymphocyte subsets will be determined in various cell mediated immune assays after separation of the cell populations in nylon wool columns, by rosetting procedures and with the use of a fluorescent activated cell sorter. The immunoregulatory circuits operative in these model systems will be analyzed in vivo and in vitro experiments. The immune reactions observed in peripheral organs will be contrasted with those exerted by the tumor infiltrating lymphoreticular cells. The information obtained in these studies will be correlated with the in vivo development of mammary tumors and the relevance of the in vitro immunolocigal reactions to the host's defenses against the oncogenic process will be evaluated in adoptive transfer immunotherapeutic procedures.